Diabetes is associated with elevations in C-reactive protein (CRP) [
46], tumour necrosis factor alpha (TNF-α) [
47], interleukin (IL)-6 [
46] and IL-8 [
48], but no differences are seen in circulating cell surface markers or coagulation markers between patients with and without diabetes in the context of sepsis. In a cohort of 1,799 patients with community-acquired pneumonia (CAP) [
49], concentrations of pro-inflammatory cytokines (TNF-α, IL-6 and IL-10), coagulation (anti-thrombin, Factor IX and thrombin–anti-thrombin complexes) and fibrinolysis (PAI-1 and D-dimer) biomarkers were similar in subjects with and without diabetes at presentation and in the first week of hospitalisation [
49]. In addition, monocyte expression of CD120a, CD120b, HLA-DR, TLR4 and TLR2 on monocytes was not different between the groups [
49]. These results are consistent with a cohort study of 830 sepsis patients, in whom plasma concentrations of IL-6 and TNF-α were elevated to the same extent in patients with and without diabetes, both at admission and at follow-up [
4]. In this second study, diabetes was not found to exacerbate the known pro-coagulant response seen in sepsis [
4]. Since sepsis and diabetes both induce a pro-inflammatory and pro-coagulant state, and since both interfere with the host response, the lack of a strong influence of diabetes on the pro-inflammatory and coagulation pathways during sepsis is remarkable. Preclinical studies in healthy volunteers have shown that acute hyperglycaemia and insulin resistance may both directly influence inflammation and coagulation [
50,
51], but these changes may not be detectable on the background of the much larger abnormalities attributable to sepsis. There is also evidence that local responses may be impaired in diabetes, e.g. levels of urinary IL-6 and IL-8 are lower in diabetic women with bacteriuria [
52]. Endothelial activation has been implicated in the pathogenesis of sepsis [
53] and diabetes is itself known to activate endothelium. A recent study of 207 sepsis patients (of whom 30% had diabetes) showed that markers of endothelial cell activation (plasma E-selectin and soluble fms-like tyrosine kinase-1 [sFLT-1]) were higher in diabetes [
54].